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Wednesday, September 5, 2012

Denisova Genome Breakthrough

There is nothing more important in DNA research than determining
those aspects of the human DNA that is truly unique to ourselves.
This allows our research focus to be targeted while those aspects
shared can be as readily studied in other species.

Stunningly we have achieved an almost complete genome for this unique
specimen. We are also been shown a new technology that will surely
be readily applied to a whole range of fossil DNA. What this surely
means is that a complete genome of the Mammoth will be achievable and
even perhaps that of the truly ancient fossils we are working with.
Jurassic Park has just become less impossible.

Knowing the code it is reasonable to replicate the code in a suitable
donor egg and generate a living specimen. Thus this is an extremely
important innovation and breakthrough. I also have little doubt that
we will soon see the Neanderthal DNA developed to the same level
using the same method.

In a stunning
technical feat, an international team of scientists has sequenced the
genome of an archaic Siberian girl 31 times over, using a new method
that amplifies single strands of DNA. The sequencing is so
complete that researchers have as sharp a picture of this ancient
genome as they would of a living person’s, revealing, for example
that the girl had brown eyes, hair, and skin. “No one thought
we would have an archaic human genome of such quality,” says
Matthias Meyer, a postdoc at the Max Planck Institute for
Evolutionary Anthropology in Leipzig, Germany. “Everyone was
shocked by the counts. That includes me.”

That precision allows
the team to compare the nuclear genome of this girl, who lived in
Siberia’s Denisova Cave more than 50,000 years ago, directly to the
genomes of living people, producing a “near-complete” catalog
of the small number of genetic changes that make us different from
the Denisovans, who were close relatives of Neandertals. “This is
the genetic recipe for being a modern human,” says team leader
Svante Pääbo, a paleogeneticist at the institute.

Ironically, this
high-resolution genome means that the Denisovans, who are represented
in the fossil record by only one tiny finger bone and two teeth, are
much better known genetically than any other ancient human —
including Neandertals, of which there are hundreds of specimens. The
team confirms that the Denisovans interbred with the ancestors of
some living humans and found that Denisovans had little genetic
diversity, suggesting that their small population waned further as
populations of modern humans expanded. “Meyer and the
consortium have set up the field of ancient DNA to be revolutionized
— again,” says Beth Shapiro, an evolutionary biologist at the
University of California, Santa Cruz, who was not part of the team.
Evolutionary geneticist Sarah Tishkoff of the University of
Pennsylvania agrees: “It’s really going to move the field
forward.”

Pääbo’s group first gave the field a jolt in May 2010 by
reporting a low-coverage sequence (1.3 copies on average) of the
composite nuclear genome from three Neandertals. They found that 1
percent to 4 percent of the DNA of Europeans and Asians, but not of
Africans, was shared with Neandertals and concluded that modern
humans interbred with Neandertals at low levels.

Just 7 months later,
the same group published 1.9 copies on average of a nuclear genome
from a girl’s pinky finger bone from Denisova Cave. They found she
was neither a Neandertal nor a modern human — although bones of
both species had been found in the cave — but a new lineage that
they called Denisovan. The team found “Denisovan DNA” in some
island Southeast Asians and concluded that their ancestors also
interbred with the ancestors of Denisovans, probably in Asia.

But these genomes were
too low quality to produce a reliable catalog of differences. Part of
the problem was that ancient DNA is fragmentary, and most of it
breaks down into single strands after it is extracted from bone.

Meyer’s breakthrough
came in developing a method to start the sequencing process with
single strands of DNA instead of double strands, as is usually done.
By binding special molecules to the ends of a single strand, the
ancient DNA was held in place while enzymes copied its sequence. The
result was a sixfold to 22-fold increase in the amount of Denisovan
DNA sequenced from a meager 10-milligram sample from the girl’s
finger. The team was able to cover 99.9 percent of the mappable
nucleotide positions in the genome at least once, and more than 92
percent of the sites at least 20 times, which is considered a
benchmark for identifying sites reliably. About half of the 31 copies
came from the girl’s mother and half from her father, producing a
genome “of equivalent quality to a recent human genome,” says
paleoanthropologist John Hawks of the University of Wisconsin,
Madison, who was not part of the team.

Now, the view of the
ancient genome is so clear that Meyer and his colleagues were able to
detect for the first time that Denisovans, like modern humans, had 23
pairs of chromosomes, rather than 24 pairs, as in chimpanzees. By
aligning the Denisovan genome with that of the reference human genome
and counting mutations, the team calculated that the Denisovan and
modern human populations finally split between 170,000 and 700,000
years ago.

The researchers also
estimated ancient Denisovan population sizes by using methods to
estimate the age of various gene lineages and the amount of
difference between the chromosomes the girl inherited from her mother
and father. They found that Denisovan genetic diversity, already low,
shrank even more 400,000 years ago, reflecting small populations at
that time. By contrast, our ancestors’ population apparently
doubled before their exodus from Africa.

The team also counted
the differences between Denisovans and chimps, and found that they
have fewer differences than do modern people and chimps. The girl’s
lineage had less time to accumulate mutations, and the “missing
evolution” suggests she died about 80,000 years ago,
although the date is tentative, says co-author David Reich, a
population geneticist at Harvard University. If this date — the
first proof that a fossil can be directly dated from its genome —
holds up, it is considerably older than the very rough dates of
30,000 to more than 50,000 years for the layer of sediment where the
fossils of Denisovans, Neandertals, and modern humans all were found.

The team says the new
genome confirms their previous findings, showing that about 3 percent
of the genomes of living people in Papua New Guinea come from
Denisovans, while the Han and Dai on mainland China have only a trace
of Denisovan DNA. Furthermore, the team determined that Papuans have
more Denisovan DNA on their autosomes, inherited equally often from
both parents, than on their X chromosomes, inherited twice as often
from the mother. This curious pattern suggests several possible
scenarios, including that male Denisovans interbred with female
modern humans, or that these unions were genetically incompatible,
with natural selection weeding out some of the X chromosomes, Reich
says.

\

The new genome also
suggests one odd result. By using the detailed Denisovan genome to
sharpen the view of their close cousins the Neandertals, the team
concludes that living East Asians have more Neandertal DNA than
Europeans have. But most Neandertal fossils are from Europe;
Paleoanthropologist Richard Klein of Stanford University in Palo
Alto, California, calls the result “peculiar.”

Most exciting to Pääbo
is the “nearly complete catalog” of differences in genes between
the groups. This includes 111,812 single nucleotides that changed in
modern humans in the past 100,000 years or so. Of those, eight were
in genes associated with the wiring of the nervous system, including
those involved in the growth of axons and dendrites and a gene
implicated in autism. Pääbo is intrigued in particular by a change
in a gene that is regulated by the so-called FOXP2 gene, implicated
in speech disorders. It is “tempting to speculate that crucial
aspects of synaptic transmission may have changed in modern humans,”
the team wrote. Thirty-four genes are associated with disease in
humans. The list suggests some obvious candidates for gene-expression
studies. “The cool thing is that it isn’t an astronomically
large list,” Pääbo says. “Our group and others will probably be
able to analyze most of them in the next decade or two.”

Back in Leipzig, the
mood is upbeat, as researchers pull fossil samples off the shelf to
test anew with “Matthias’s method.” First on Pääbo’s list:
Neandertal bone samples, to try to produce a Neandertal genome to
rival that of the little Denisovan girl.

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Apr 2017 - 4.1 Mil Pg Views, March 2013 - Posted my paper introducing CLOUD COSMOLOGY & NEUTRAL NEUTRINO rigorously described, September 2010 I am pleased to report that my essay titled A NEW METRIC WITH APPLICATIONS TO PHYSICS AND SOLVING CERTAIN HIGHER ORDERED DIFFERENTIAL EQUATIONS' has been published in Physics Essays(AIP) and appeared in their June 2010 quarterly. 40 years ago I took an honors degree in applied mathematics from the University of Waterloo. My interest was Relativity and my last year there saw me complete a 900 level course under Hanno Rund on his work in relativity,as well as differential geometry(pure math) and of course analysis. I continued researching new ideas and knowledge since that time and I have prepared a book for publication titled Paradigms Shift&. I maintain my blog as a day book and research tool to retain data and record impressions and interpretations on material read. Do join my blog and receive Four items of interest daily Monday through Saturday.